Sex Specificity Research Articles

Sex-specific association between schizophrenia polygenic risk and subclinical schizophrenia-related traits

BackgroundAccording to the dimensional view of psychiatric disorders, psychosis is expressed as a continuum in the general population. However, the investigation of the putative genetic aetiological continuity between its clinical and subclinical phenotypes has yielded mixed results. We aimed to replicate previous findings regarding the association of polygenic risk for schizophrenia with subclinical traits (i.e., schizotypy traits and psychotic-like experiences), and to examine the role of sex in this association in a large nonclinical sample. MethodsThe Multidimensional Schizotypy Scale and the Community Assessment of Psychic Experiences were assessed in 919 nonclinical participants. Polygenic Risk Scores for schizophrenia (SZ-PRSs) were computed using the PRS-CS method based on the latest genome-wide association study of schizophrenia. Summary statistics derived from the total GWAS sample and stratified by sex were used. Linear regression analyses tested the associations of the SZ-PRSs with the psychometric variables, both in the total sample and by sex. ResultsNo associations were found between the SZ-PRSs and the positive, negative or disorganized dimensions of schizotypy in the total sample. Likewise, no associations were found with psychotic-like experiences. However, the sex-stratified analyses revealed a male-specific association with positive schizotypy. Similar results were obtained with the PRSs derived from the sex-stratified summary statistics. DiscussionOur results are consistent with the lack of clear evidence of an association between SZ common genetic risk and its subclinical phenotypes. Nevertheless, the male-specific association found suggests that this PRS might explain better the male phenotype, as reported in previous studies. Future studies should put a focus on the role of sex in this association to unravel its sex specificities.

High-fat and High-sucrose Diet-induced Hypothalamic Inflammation Shows Sex Specific Features in Mice.

Hypothalamic inflammation underlies diet-induced obesity and diabetes in rodent models. While diet normalization largely allows for recovery from metabolic impairment, it remains unknown whether long-term hypothalamic inflammation induced by obesogenic diets is a reversible process. In this study, we aimed at determining sex specificity of hypothalamic neuroinflammation and gliosis in mice fed a fat- and sugar-rich diet, and their reversibility upon diet normalization. Mice were fed a 60%-fat diet complemented by a 20% sucrose drink (HFHSD) for 3 days or 24 weeks, followed by a third group that had their diet normalized for the last 8 weeks of the study (reverse diet group, RevD). We determined the expression of pro- and anti-inflammatory cytokines, and of the inflammatory cell markers IBA1, CD68, GFAP and EMR1 in the hypothalamus, and analyzed morphology of microglia (IBA-1+ cells) and astrocytes (GFAP+ cells) in the arcuate nucleus. After 3 days of HFHSD feeding, male mice showed over-expression of IL-13, IL-18, IFN-γ, CD68 and EMR1 and reduced expression of IL-10, while females showed increased IL-6 and IBA1 and reduced IL-13, compared to controls. After 24 weeks of HFHSD exposure, male mice showed a general depression in the expression of cytokines, with prominent reduction of TNF-α, IL-6 and IL-13, but increased TGF-β, while female mice showed over-expression of IFN-γ and IL-18. Furthermore, both female and male mice showed some degree of gliosis after HFHSD feeding for 24 weeks. In mice of both sexes, diet normalization after prolonged HFHSD feeding resulted in partial neuroinflammation recovery in the hypothalamus, but gliosis was only recovered in females. In sum, HFHSD-fed mice display sex-specific inflammatory processes in the hypothalamus that are not fully reversible after diet normalization.

Species-level verification of Phascolarctobacterium association with colorectal cancer.

We have previously demonstrated an association between increased abundance of Phascolarctobacterium and colorectal cancer (CRC) and adenomas in two independent Norwegian cohorts. Here we seek to verify our previous findings using new cohorts and methods. In addition, we characterize lifestyle and sex specificity, the functional potential of the Phascolarctobacterium species, and their interaction with other microbial species. We analyze Phascolarctobacterium with 16S rRNA sequencing, shotgun metagenome sequencing, and species-specific qPCR, using 2350 samples from three Norwegian cohorts-CRCAhus, NORCCAP, and CRCbiome-and a large publicly available data set, curatedMetagenomicData. Using metagenome-assembled genomes from the CRCbiome study, we explore the genomic characteristics and functional potential of the Phascolarctobacterium pangenome. Three species of Phascolarctobacterium associated with adenoma/CRC were consistently detected by qPCR and sequencing. Positive associations with adenomas/CRC were verified for Phascolarctobacterium succinatutens and negative associations were shown for Phascolarctobacterium faecium and adenoma in curatedMetagenomicData. Men show a higher prevalence of P. succinatutens across cohorts. Co-occurrence among Phascolarctobacterium species was low (<6%). Each of the three species shows distinct microbial composition and forms distinct correlation networks with other bacterial taxa, although Dialister invisus was negatively correlated to all investigated Phascolarctobacterium species. Pangenome analyses showed P. succinatutens to be enriched for genes related to porphyrin metabolism and degradation of complex carbohydrates, whereas glycoside hydrolase enzyme 3 was specific to P. faecium.IMPORTANCEUntil now Phascolarctobacterium has been going under the radar as a CRC-associated genus despite having been noted, but overseen, as such for over a decade. We found not just one, but two species of Phascolarctobacterium to be associated with CRC-Phascolarctobacterium succinatutens was more abundant in adenoma/CRC, while Phascolarctobacterium faecium was less abundant in adenoma. Each of them represents distinct communities, constituted by specific microbial partners and metabolic capacities-and they rarely occur together in the same patients. We have verified that P. succinatutens is increased in adenoma and CRC and this species should be recognized among the most important CRC-associated bacteria.

Sex-specific effect of maternal thyroid peroxidase antibody exposure during pregnancy on 5- to 6-year-old children's cardiometabolic risk score: the Ma'anshan birth cohort study.

To explore the association between maternal thyroid peroxidase antibody (TPOAb) exposure and 5- to 6-year-old children's cardiometabolic risk (CMR). A total of 2129 mother-child pairs were recruited from the Ma'anshan Birth Cohort (MABC) study. Serum TPOAb was retrospectively measured in pregnant women using an electrochemiluminescence immunoassay. CMR score was evaluated by the serum glycolipids, blood pressure, and waist circumference for children aged 5-6 years. Growth mixture modelling was used to fit trajectories of TPOAb levels throughout pregnancy. Multiple linear regression models and logistic regression models were used for statistical analyses. Two thousand one hundred twenty-nine mother-child pairs (mean [SD] age, 26.6 [3.6] years) were enrolled for the final study. Maternal TPOAb exposure in the first trimester increased children's overall CMR, glucose level, HOMA-IR, triglyceride level, boys' overall CMR, boys' glucose level, and girls' glucose level. TPOAb exposure in the first trimester was also associated with lower boys' high-density lipoprotein cholesterol (HDL-C) level. In the second trimester, maternal TPOAb exposure was positively associated with children's triglyceride level. Compared with low TPOAb trajectory, children with high maternal TPOAb trajectory had an increased risk of developing high CMR (OR = 3.40; 95% CI, 1.30-8.90), hyperglycemia (OR = 5.20; 95% CI, 2.20-12.28), insulin-resistance (adjusted OR = 2.12; 95% CI, 1.10-4.07), and hypertriglyceridemia (OR = 2.55; 95% CI, 1.06-6.14). The first trimester of pregnancy is a critical period for maternal TPOAb exposure to affect CMR in children, with some sex specificity, mainly to the detriment of boys.

Sex Differences in Mouse Models of Voluntary Alcohol Drinking and Abstinence-Induced Negative Emotion

Alcohol Use Disorder (AUD) is a growing problem worldwide, causing an incredible burden on health and the economy. Though AUD impacts people of all backgrounds and demographics, increasing evidence has suggested robust sex differences in alcohol drinking patterns and AUD-induced negative emotionality or hyperkatifeia. Rates of problematic drinking have significantly risen among women, and women face more severe negative emotional consequences in abstinence such as increased risk of comorbidity with an anxiety or mood disorder and more severe symptoms of depression. As such, a bevy of preclinical literature using contingent methods of alcohol (ethanol) consumption has amassed in recent years to better understand sex as a biological variable in alcohol drinking and abstinence-induced negative emotionality. Mice are widely used to model alcohol drinking, as they are conducive to genetic manipulation strategies, and many strains will voluntarily consume alcohol. Sex-specific results from these mouse studies, however, have been inconsistent. Therefore, this review aims to summarize the current knowledge on sex differences in AUD-related contingent ethanol drinking and abstinence-induced negative emotionality in mice. Various contingent mouse drinking models and negative emotional-based behavioral paradigms are introduced and subsequently discussed in the context of sex differences to show increasing indications of sex specificity in mouse preclinical studies of AUD. With this review, we hope to inform future research on potential sex differences in preclinical mouse models of AUD and provide mounting evidence supporting the need for more widespread inclusion of preclinical female subjects in future studies.

Widespread Distribution of Luteinizing Hormone/Choriogonadotropin Receptor in Human Juvenile Angiofibroma: Implications for a Sex-Specific Nasal Tumor.

Juvenile angiofibroma (JA) is a rare, sex-specific, and highly vascularized nasal tumor that almost exclusively affects male adolescents, but its etiology has been controversial. The G protein-coupled hormone receptor LHCGR [luteinizing hormone (LH)/choriogonadotropin (hCG) receptor] represents a promising new candidate for elucidating the underlying mechanisms of sex specificity, pubertal manifestation, and JA progression. We used highly sensitive RNAscope technology, together with immunohistochemistry, to investigate the cellular expression, localization, and distribution of LHCGR in tissue samples from JA patients. Our results provide evidence for LHCGR expression in subsets of cells throughout JA tissue sections, with the majority of LHCGR+ cells located in close vicinity to blood vessels, rendering them susceptible to endocrine LH/hCG signaling, but LHCGR+ cells were also detected in fibrocollagenous stroma. A majority of LHCGR+ cells located near the vascular lumen co-expressed the neural crest stem cell marker CD271. These results are intriguing as both LH and hCG are produced in a time- and sex-dependent manner, and are known to be capable of inducing cell proliferation and angiogenesis. Our results give rise to a new model that suggests endocrine mechanisms involving LHCGR and its ligands, together with autocrine and paracrine signaling, in JA vascularization and cell proliferation.

Antioxidant Response of Maternal and Fetal Rat Liver to Selenium Nanoparticle Supplementation Compared to Sodium Selenite: Sex Differences between Fetuses.

To compare the effects of organic selenium nanoparticles (SeNPs, Se0) and inorganic sodium selenite (NaSe, Na2SeO3, Se4+) on the antioxidant response in maternal and fetal rat liver, pregnant females were treated with two forms of selenium (Se) at equivalent doses during gestation (0.5 mg SeNPs or 0.5 mg NaSe/kg body weight/day). Structural parameters of the liver of gravid females and their fetuses were examined in a sex-specific manner. The oxidative stress parameters superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), glutathione S-transferase (GST), total glutathione (GSH) and sulfhydryl groups (SH) were established. In addition, the Se concentration was determined in the blood, liver, urine and feces of the gravid females and in the liver of the fetuses. The structure of the liver of gravid females remained histologically the same after supplementation with both forms of Se, while the oxidative stress in the liver was significantly lower after the use of SeNPs compared to NaSe. Immaturity of fetal antioxidant defenses and sex specificity were demonstrated. This study provides a detailed insight into the differences in the bioavailability of the nano form of Se compared to sodium selenite in the livers of pregnant females and fetuses.

The role of TrkB signaling-mediated synaptic plasticity in the antidepressant properties of catalpol, the main active compound of Rehmannia glutinosa Libosch.

Ethnopharmacological relevanceRehmannia glutinosa Libosch. (RGL) is a famous ethnic medicine contained in antidepressant Chinese medicine formulas and is traditionally clinically used for depression. We have recently confirmed that RGL enhanced synaptic plasticity in a mouse model of Chinese medical syndrome and that catalpol may be the representatively pharmacological component responsible for its improvement in synaptic plasticity and treatment of depression. Impaired synaptic plasticity is closely linked to major depression. Tyrosine kinase receptor B (TrkB) signaling has recently been discovered as a key pathway for synaptic plasticity improvement and antidepressant discovery. However, to date, it is unknown whether the target of catalpol to improve synaptic plasticity involves TrkB and whether its antidepressant mechanism involves synaptic plasticity mediated by TrkB signaling. Aim of studyThis study aims to elucidate the potential antidepressant target and mechanisms of catalpol, the main active compound of RGL, through TrkB signaling-mediated synaptic plasticity. Materials and methodsWe have recently predicted through molecular networking strategy (including network pharmacology, molecular docking, and molecular dynamics simulation) that catalpol may exert its antidepressant effects by regulating TrkB signaling and thus modulating essential synaptic plasticity proteins. Then, this study used classic behavioral tests, targeted diagnostic reagents, Nissl and Golgi staining, immunohistochemical analysis, immunofluorescence analysis, Western blot, enzyme-linked immunosorbent assay, and Real-time PCR to confirm the potential target and signaling of catalpol to improve synaptic plasticity for the treatment of depression. ResultsThe data showed that catalpol could improve synaptic plasticity and depressive behaviors, and its action pathway was predicted to involve TrkB signaling. Subsequently, the blockade of TrkB abolished the improvement of synaptic plasticity by catalpol and its antidepressant properties, which validated that TrkB signaling was the key pathway for catalpol to improve synaptic plasticity and exert antidepressant properties. Inhibition of COX-2 was likely to be a necessary facilitator for the antidepressant efficacy of catalpol via the TrkB target and TrkB-mediated synaptic plasticity. ConclusionTrkB signaling-mediated synaptic plasticity plays a key role in the antidepressant properties of catalpol. This study provides critical information for the development of new and targeted antidepressant therapies or treatment strategies by catalpol. However, considering the existence of sex differences in depression (female depression is 2–3 times than that of males) and not exploring the antidepressant sex specificity of catalpol is a limitation, we will investigate the sex specificity of the antidepressant effects and molecular mechanisms of catalpol on sex-specific animals in the future to provide a preclinical basis for more accurate and targeted medication of catalpol.

Sex-specific associations of plasma neutrophil gelatinase-associated lipocalin (NGAL) with cognition in patients with drug-naïve schizophrenia

This present study aimed to investigate the sex-specific association of plasma neutrophil gelatinase-associated lipocalin (NGAL) with cognition in drug-naïve schizophrenia patients for the first time. A total of 204 participants in this study, including 137 drug-naïve schizophrenia (DNS) patients and 67 healthy controls (HCs). All participants completed the Measurements and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB), and were collected fasting venous blood for NGAL measurement. DNS patients also complete the Positive and Negative Syndrome Scale (PANSS). Partial correlation analysis and multiple linear regression were used to explore sex-specific associations between NGAL and cognition. All dimensions of MCCB scores were significantly lower in both male and female DNS patients than HCs. Sex differences were significant in cognitive performance in both DNS patients and HCs. Female DNS patients experienced poorer working memory and reason& problem solving than male patients. Female HCs performed a better attention/vigilance and visual learning, a poorer reason& problem solving than male HCs. In patients with DNS, NGAL levels were negatively associated with positive subscale of PANSS and positively associated with working memory and visual learning only in female. However, there was no significant correlation between NGAL levels and all cognitive tests in both male and female HCs. Regression model showed that higher level of NGAL was an independent protective factor for cognitive performance in female patients with DNS, whereas there was no such role in male patients. Our findings suggest sex specificity between NGAL levels and cognitive performance in DNS patients.

TNFR1/p38αMAPK signaling in Nex + supraspinal neurons regulates estrogen-dependent chronic neuropathic pain

Upregulation of soluble tumor necrosis factor (sTNF) cytokine signaling through TNF receptor 1 (TNFR1) and subsequent neuronal hyperexcitability are observed in both animal models and human chronic neuropathic pain (CNP). Previously, we have shown that estrogen modulates sTNF/TNFR1 signaling in CNP, which may contribute to female prevalence of CNP. The estrogen-dependent role of TNFR1-mediated supraspinal neuronal circuitry in CNP remains unknown. In this study, we interrogated the intersect between supraspinal TNFR1 mediated neuronal signaling and sex specificity by selectively removing TNFR1 in Nex + neurons in adult mice (NexCreERT2::TNFR1f/f). We determined that mechanical hypersensitivity induced by chronic constriction injury (CCI) decreases over time in males, but not in females. Subsequently, we investigated two downstream pathways, p38MAPK and NF-κB, important in TNFR1 signaling and injury response. We detected p38MAPK and NF-κB activation in male cortical tissue; however, p38MAPK phosphorylation was reduced in NexCreERT2::TNFR1f/f males. We observed a similar recovery from acute pain in male mice following CCI when p38αMAPK was knocked out of supraspinal Nex + neurons (NexCreERT2::p38αMAPKf/f), while chronic pain developed in female mice. To explore the intersection between estrogen and inflammation in CNP we used a combination therapy of an estrogen receptor β (ER β) inhibitor with a sTNF/TNFR1 or general p38MAPK inhibitor. We determined both combination therapies lends therapeutic relief to females following CCI comparable to the response evaluated in male mice. These data suggest that TNFR1/p38αMAPK signaling in Nex + neurons in CNP is male-specific and lack of therapeutic efficacy following sTNF inhibition in females is due to ER β interference. These studies highlight sex-specific differences in pathways important to pain chronification and elucidate potential therapeutic strategies that would be effective in both sexes.

Differences in help-seeking behaviour between males and females with multiple pelvic floor symptoms: A qualitative study

BackgroundPelvic floor symptoms (PFS) are common and frequently co-occur, but few patients seek help despite negative effects on their quality of life. Moreover, most studies assessing help-seeking behaviour have only focused on a single PFS. AimWe aimed to explore the barriers to and facilitators of help-seeking behaviour in males and females with at least two PFS. Design and SettingThis interview-based study included participants by age and symptoms (number and type) from a larger group taking part in a survey on PFS in the general population. MethodTwo researchers independently encoded and analyzed the semi-structured interviews, which continued to saturation for both the male and female cohorts. ResultsOf the 25 participants (13 male and 12 female), 9 sought help for all PFS, 10 did not seek help for any PFS, and 6 sought help for some PFS. We identified themes in domains related to the patient, healthcare professional, environment, and symptoms. Although most themes applied to both sexes, some had greater sex specificity. ConclusionMales and females have more similarities than differences in help-seeking behaviour. Healthcare providers should know that patients who seek help for one symptom probably have multiple PFS that the patient has not reported.

Sex disparities in cardiogenic shock: Insights from the FRENSHOCK registry

BackgroundCardiogenic shock (CS) is the most severe form of acute heart failure. Discrepancies have been reported between sexes regarding delays, pathways and invasive strategies in CS complicating acute myocardial infarction. However, effect of sex on the prognosis of unselected CS remains controversial. ObjectivesThe aim was to analyze the impact of sex on aetiology, management and prognosis of CS. MethodsThe FRENSHOCK registry included all CS admitted in 49 French Intensive Care Units (ICU) and Intensive Cardiac Care Units (ICCU) between April and October 2016. ResultsAmong the 772 CS patients included, 220 were women (28.5%). Women were older, less smokers, with less history of ischemic cardiac disease (20.5% vs 33.6%) than men. At admission, women presented less cardiac arrest (5.5 vs 12.2%), less mottling (32.5 vs 41.4%) and higher LVEF (30 ± 14 vs 25 ± 13%). Women were more often managed via emergency department while men were directly admitted at ICU/ICCU. Ischemia was the most frequent trigger irrespective of sex (36.4% in women vs 38.2%) but women had less coronary angiogram and PCI (45.9% vs 54% and 24.1 vs 31.3%, respectively). We found no major difference in medication and organ support. Thirty-day mortality (26.4 vs 26.5%), transplant or permanent assist device were similar in both sexes. ConclusionDespite some more favorable parameters in initial presentation and no significant difference in medication and support, women shared similar poor prognosis than men. Further analysis is required to cover the lasting gap in knowledge regarding sex specificities to distinguish between differences and inequalities. NCT02703038

Where are we in the implementation of tissue-specific epigenetic clocks?

Introduction: DNA methylation clocks presents advantageous characteristics with respect to the ambitious goal of identifying very early markers of disease, based on the concept that accelerated ageing is a reliable predictor in this sense. Methods: Such tools, being epigenomic based, are expected to be conditioned by sex and tissue specificities, and this work is about quantifying this dependency as well as that from the regression model and the size of the training set. Results: Our quantitative results indicate that elastic-net penalization is the best performing strategy, and better so when-unsurprisingly-the data set is bigger; sex does not appear to condition clocks performances and tissue specific clocks appear to perform better than generic blood clocks. Finally, when considering all trained clocks, we identified a subset of genes that, to the best of our knowledge, have not been presented yet and might deserve further investigation: CPT1A, MMP15, SHROOM3, SLIT3, and SYNGR. Conclusion: These factual starting points can be useful for the future medical translation of clocks and in particular in the debate between multi-tissue clocks, generally trained on a large majority of blood samples, and tissue-specific clocks.

Diversity, Composition, and Specificity of the Philaenus spumarius Bacteriome.

Philaenus spumarius (Linnaeus, 1758) (Hemiptera, Aphrophoridae) was recently classified as a pest due to its ability to act as a vector of the phytopathogen Xylella fastidiosa. This insect has been reported to harbour several symbiotic bacteria that play essential roles in P. spumarius health and fitness. However, the factors driving bacterial assemblages remain largely unexplored. Here, the bacteriome associated with different organs (head, abdomen, and genitalia) of males and females of P. spumarius was characterized using culturally dependent and independent methods and compared in terms of diversity and composition. The bacteriome of P. spumarius is enriched in Proteobacteria, Bacteroidota, and Actinobacteria phyla, as well as in Candidatus Sulcia and Cutibacterium genera. The most frequent isolates were Curtobacterium, Pseudomonas, and Rhizobiaceae sp.1. Males display a more diverse bacterial community than females, but no differences in diversity were found in distinct organs. However, the organ shapes the bacteriome structure more than sex, with the Microbacteriaceae family revealing a high level of organ specificity and the Blattabacteriaceae family showing a high level of sex specificity. Several symbiotic bacterial genera were identified in P. spumarius for the first time, including Rhodococcus, Citrobacter, Halomonas, Streptomyces, and Providencia. Differences in the bacterial composition within P. spumarius organs and sexes suggest an adaptation of bacteria to particular insect tissues, potentially shaped by their significance in the life and overall fitness of P. spumarius. Although more research on the bacteria of P. spumarius interactions is needed, such knowledge could help to develop specific bacterial-based insect management strategies.

Sex and age specificities of the dynamics of anthropometric indicators characterizing obesity (according to a prospective epidemiological research)

Background. Overweight and obesity significantly increase the risk of premature death and the development of chronic diseases. Many anthropometric indices have been developed to verify obesity, although the best among them still remains undetermined.The aim. To determine the sex and age specificities of the dynamics of anthropometric indicators characterizing obesity.Materials and methods. The program was implemented in the period from 2015 to 2020. It provided for the implementation of a sample research. The baseline research included 1,124 women and 476 men. The average age was 54.9 ± 9.75 years and 52.6 ± 10.0 years, respectively. To identify gender specificities, all participants were divided into three age groups: 35–49 years old, 50–59 years old, and 60–70 years old. The observation period was 3 years. To determine the level of visceral fat, the VS-532 fat mass analyzer (Tanita Health Equipment HK Ltd., Hong Kong) was used. Body mass index (BMI), waist-hip index (WV/HV), visceral obesity index (VOI) were also calculated. Statistical processing of the results was carried out using the program Statistica 6.0 (StatSoft Inc., USA).Results. New cases of obesity developed in 30.6 % of the surveyed. There was an increase in the prevalence of obesity according to the criteria of WV (by 8.9 %) and VFL (by 5.4 %) and a decrease in the number of people who are obese according to WV/HV – by 4.2 %. Of all the indicators, only VOI showed a statistically significant decrease in the mean values over the observed period, while BMI, WV and VFL showed an increase.Conclusions. It is necessary to apply various criteria for the diagnosis of obesity, since individual indices are not able to fully reflect the gender and age specificities of the distribution of fat in the body

French National Trends in Neurodevelopmental and Mental Health-Related Healthcare Center Visits among Youth, 2014-2022: Towards Sex Specificities in the Care Pathway

Background: Neurodevelopmental disorders (NDD) and mental health (MH)-related conditions among children and adolescents, represent a global public health burden, that was worsened by the COVID-19 pandemic due to disruptions in access to healthcare, support services, and increased stressors exacerbating symptoms and challenges. However, few studies have examined in France, NDD and MH’s diagnoses and care pathway in youth attending public healthcare center (HCC) services. Methods: An annual cross-sectional analysis was performed in youth aged 0 to 17 years on health information, that were extracted from the French PMSI database (DIAMANT database) between January 1, 2014, and December 31, 2022, using the MH-related ICD-10 diagnosis codes, including NDD, mood-, behavior-, anxiety-, and other-disorders (sleep and eating). Trends in healthcare center visits for NDD and MH-related conditions, were evaluated according to age, sex, diagnoses, and care pathway over the 10-year period using ANOVAs. Findings: Out of the 17,707,806 total HCC-visits across a 10-year period, 289,382 visits (1,6%) were related to youth with diagnoses for NDD or MH disorders of the study interest. Among them, 57% were girls and 43% boys. The total number of pediatric HCC-visits related to NDD and MH has remained stable from 2014 to 2022. However, the proportion of visits has doubled for adolescent girls with internalizing disorders (anxiety and mood) while a 5-fold decrease in the proportion of visits for NDD, was observed for boys aged 0 to 12 years. The HCC-admission mainstream for internalizing disorders was the emergency department and was “home” for the NDD. While the HCC-discharge accounted for 9% of patients being hospitalized, most of them were sent home (90.7%) with a strong age- and sex-specificities. Interpretation: Over the last 10 years, the proportion of HCC visits for NDD and MH remained stable, but strong age- and sex-effects were found on diagnoses visits and care pathway. These findings are essential to improve emergency and outpatient service capacity dedicated to youth. They could help European and national policies to patient-tailor care pathway depending on sex and diagnosis from screening, interventions, and monitoring during this sensitive period of development.

Evolution of Microglia.

Microglial cells are unique tissue-resident macrophages located in the parenchyma of the central nervous system (CNS). A recent comparative transcriptional study on microglia across more than 20 species from leach across chicken and many more up to humans revealed multiple conserved features. The results indicate the imperative role of microglia over the last 500 million years (Geirsdottir et al. Cell 181:746, 2020). Improved understanding of microglial evolution provides essential insights into conserved and divergent microglial pathways and will have implications for future development of microglia-based therapies to treat CNS disorders. Not only therapeutic approaches may be rethought, but also the understanding of sex specificity of the immune system within the CNS needs to be renewed. Besides revealing the highly detailed characteristics of microglia, the former paradigm of microglia being the only CNS-resident immune cells was outdated by the identification of CNS-associated macrophages (CAMs) as CNS interface residents, who, most likely, accompanied microglia in evolution over the past million years.

Epigenetics of the far northern Yakutian population

BackgroundYakuts are one of the indigenous populations of the subarctic and arctic territories of Siberia characterized by a continental subarctic climate with severe winters, with the regular January average temperature in the regional capital city of Yakutsk dipping below − 40 °C. The epigenetic mechanisms of adaptation to such ecologies and environments and, in particular, epigenetic age acceleration in the local population have not been studied before.ResultsThis work reports the first epigenetic study of the Yakutian population using whole-blood DNA methylation data, supplemented with the comparison to the residents of Central Russia. Gene set enrichment analysis revealed, among others, geographic region-specific differentially methylated regions associated with adaptation to climatic conditions (water consumption, digestive system regulation), aging processes (actin filament activity, cell fate), and both of them (channel activity, regulation of steroid and corticosteroid hormone secretion). Further, it is demonstrated that the epigenetic age acceleration of the Yakutian representatives is significantly higher than that of Central Russia counterparts. For both geographic regions, we showed that epigenetically males age faster than females, whereas no significant sex differences were found between the regions.ConclusionsWe performed the first study of the epigenetic data of the Yakutia cohort, paying special attention to region-specific features, aging processes, age acceleration, and sex specificity.

Sex-specific responses of Ruditapes philippinarum to ocean acidification following gonadal maturation

Ocean acidification (OA) can seriously affect marine bivalves at different levels of biological organization, generating widespread consequences on progeny recruitment and population maintenance. Yet, few effort has been devoted to elucidating whether female and male bivalves respond differentially to OA in their reproductive seasons. Here, we estimated differences in physiological responses of female and male Manila clams (Ruditapes philippinarum) to OA during gonadal maturation. In comparison to OA-stressed male clams, females significantly depressed activities in enzymes related to energy metabolism (NKA, T-ATP), antioxidant defence (SOD and MDA), and non-specific immune function (ACP), and downregulated expression of AMPK that plays a key role in cellular metabolism, indicating that sex did significantly affect responses of R. philippinarum to OA. Such sex-based differences can be likely couched in energetic terms, given the much more energetically expensive cost of egg production than that of sperms. These results indicate that sex-specific responses to OA during reproductive seasons do exist in marine bivalves, and therefore accounting for such sex specificity is of paramount importance when projecting population sustainability and formulating conservation strategies in an acidifying ocean.

Sex Differences in Complex Posttraumatic Stress Disorder Network among Chinese Young Adults.

Evidence suggests that sex differences commonly occur in trauma-related disorders. The current study aims to explore sex differences in complex posttraumatic stress disorder (CPTSD) symptom networks among Chinese young adults with childhood trauma. The current study utilized a representative sample of college students in Beijing and included 1416 participants (409 men and 907 women) who had childhood trauma experience. CPTSD symptoms were evaluated using the International Trauma Questionnaire. Regularized partial correlation network analysis and Bayesian network analysis were used to estimate the network structure and possible causality of CPTSD symptoms for both sexes. Male and female CPTSD symptom networks had differences in strength centrality and bridge centrality. Nightmares and feelings of failure had the highest strength centrality, and long-term upset and nightmares had the highest bridge centrality for men. Hypervigilance and feelings of failure had the highest strength centrality, and long-term upset and exaggerated startle response had the highest bridge centrality for women. The current study provides the first evidence of sex differences in the CPTSD symptom network among Chinese young adults with childhood trauma. Young men and women differed in highly central symptoms, which may speak to sex specificity in the main manifestations of CPTSD symptoms.